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PubMed1992

Evolution of clonality and invasive behavior of Epstein-Barr virus immortalized lymphoblastoid cell lines in SCID mice brains.

BACKGROUND: Recently established Epstein-Barr virus immortalized lymphoblastoid cell lines express polyclonal immunoglobulins, are diploid, and grow into invasive tumors when injected intracerebrally into mice with severe combined immunodeficiency (SCID). It is unclear whether clonal selection of neurotropic cell lines occurs during long-term growth in the brain and the effect of this selection on brain invasiveness. EXPERIMENTAL DESIGN: Epstein-Barr immortalized lymphoblastoid cell lines from a normal Epstein-Barr negative donor were serially passaged seven times intracerebrally within groups of SCID/SCID CB 17 mice. Each cell line was injected into five or more animals during each passage. Clonality of the rescued cell lines, genotype, and brain invasiveness were examined. RESULTS: All mice developed extensive intracerebral lymphoproliferative disease within 10-18 days after injection. Intracerebral, subarachnoid, intraventricular, and perivascular lymphoid lesions were noted. Infiltrates were similar in all animals studied regardless of the passage number. Clonal B cell populations were detectable in lesions after the first passage by Southern blot hybridization using JH probe. Immunohistochemically, polyclonal tumors were seen initially, but after the fourth passage, monoclonal cytoplasmic immunoglobulin was predominantly expressed by all tumors. Minor bands seen in the early passages disappeared subsequently. Random chromosomal abnormalities appeared in the rescued cell lines after the third passage; however, after the sixth passage, the abnormalities became more consistent. Clonability in agarose was very low initially in both cell lines and increased significantly after the sixth passage. CONCLUSIONS: These experiments demonstrate that within the immunoprivileged conditions of the SCID mouse brain, the evolution of Epstein-Barr immortalized lymphocytes from polyclonal to oligo- and monoclonal cell lines with chromosomal abnormalities occurs very early. This evolution is not paralleled by increased invasiveness in vivo.

Animals↗
PubMed1991

[Occupational asthma: current and future perspectives. The point of view of an expert].

Occupational asthma remains a difficult problem for physicians and for experts. The prevalence of occupational asthma is underestimated and depends on industrial agent and conditions of work. Diagnosis is made based on detailed description of the patient's work environment, on skin and serological tests, and on lung function tests including non-specific bronchial provocation tests. Rhinomanometry, and peak flow rate measurements may also be useful. Bronchial provocation tests should be performed by experienced staff in a hospital setting with facilities for resuscitation. The prognosis of occupational asthma is variable: --some patients with short and limited exposure may fully recover if their disease is early recognized and appropriate measures are taken; --however, many patients do not recover completely after removal of the responsible agents. Clinical symptoms and bronchial hyperreactivity persist and respiratory insufficiency may develop. The patterns of occupational asthma are changing rapidly, in parallel with industrial evolution: nowadays, bakers's asthma is less frequent than it used to be. Asthma triggered by wood dust and in particular western red cedar (which is exported all over the world) is increasingly recognized. Isocyanates and, in particular toluene isocyanate, are widely used in plastics and paints. Preventive measures have succeeded in decreasing the incidence of asthma caused by exposure to isocyanates. Computer industry has recently developed in many countries. It requires the use of numerous hazardous and highly toxic materials that are potentially responsible for occupational asthma; attention should be given to respiratory diseases especially in industrializing countries (such as Eastern Asian countries). Preventive measures include safety rules, replacement of harmful materials by less toxic agents and detection of susceptible workers. Regulation must be defined under experts' control to continuously match the rapid changes in modern industry.

Asthma↗
PubMedDate not supplied

[Transmission and expression of malignancy in somatic hybrid cell lines (hamster/hamster, mouse/mouse, hamster/mouse)].

Various characteristics of transformation were studied in subclones isolated from a hybrid cell line obtained by fusion of two Chinese hamster sub-lines having the same origin but presenting different properties, particularly in respect to heterotransplantability. Different subclones were obtained by cloning on semisoft agar. Transplantability, plating efficiency, agglutinability by concanavalin A and actinomycin D resistance were studied in parallel with the evolution of the karyotype to try to find a correlation between these various parameters. A relationship seems to exist between a chromosome marker arising in the hybrid and the percentage of tumours. The second part of this work dealth with the study of intra and interspecies hybrids, one of the parents of which was a normal, fibroblastic cell and the other of which contained the polyoma virus genome. In the hybrid cell this viral genome was expressed at several levels. Firstly, in the formation of specific polyoma virus-induced antigens and secondaryly, in surface properties normally considered related to the expression of tumorigenicity. Nevertheless, tumour development was repressed. Though the presence of characteristic antigens seemed necessary for the expression of malignant transformation, presence alone was not sufficient to induce malignant transformation of the cell. The study of inter-species mouse/hamster hybrids showed that this situation is not general. For this we examined the properties of hybrid cells between, on the one hand, a mouse tumorigenic cell bearing polyoma virus genetic information and, on the other, non-tumorigenic mouse or hamster cell. In this case the complete hamster genome could bot repress malignancy whereas a few mouse chromosomes sufficed to code for the expression of virus-induced tumour antigens and various malignant properties. It may be hoped that these hybrids could be used to pin-point the chromosome localization of the genetic factors of malignancy and could be used in immunoprotection studies or immunotherapy research.

Agglutination↗
PubMed1989

[The nursing dimension in palliative care].

In this 250-bed general hospital, nursing care for the dying focuses not on recovery but on self-actualization. In a broader context, patients also benefit from nursing's theory-based approach. A parallel between the evolution of the patient and the nursing process is established.

Adult↗
PubMed1988

Teaching medical professionals to retrieve and manage medical information.

Popularity of the personal computer has prompted physician interest in direct access to the medical literature from sophisticated electronic data retrieval systems. This paper describes the educational programs developed by the library at the George Washington University Medical Center in response to this interest and growing national trend. As a result of these programs, the role of the librarian has changed permanently. Librarians are now perceived by faculty as educational specialists and information consultants. The evolution in libraries parallels the technological changes taking place in other biomedical communications units. The authors recommend the positive outcomes from adapting traditional roles to meet user's needs in a changing environment.

Humans↗
PubMed1984

Thymic nurse cells and thymic repopulation after whole body sublethal irradiation in mice.

Thymic Nurse Cells (TNCs) are lymphoepithelial complexes which are thought to play a role in the early stages of the intrathymic differentiation pathway. Therefore, their repopulation kinetics were analyzed in mice after sublethal whole-body irradiation. Changes of the number of TNCs per thymus were parallel with the evolution of the whole thymocyte population. Particularly, a first wave of TNCs restoration was followed by a secondary depletion and a final recovery. This suggests that TNCs restoration is related to the proliferating progeny of intrathymic radioresistant thymocytes. When normal bone marrow cells were grafted intravenously after irradiation, no secondary depletion was found. This pattern of restoration was obviously related to thymic repopulation by cells which were derived from the inoculated bone marrow. Homing studies with FITC labelled bone marrow cells showed that inoculated bone marrow cells did not penetrate TNCs early after irradiation. Later on, when immigrant cells started to proliferate, they were found preferentially within TNCs before spreading in the whole thymus. The results indicate that interactions between immature thymocytes and epithelial cells within TNCs are critical for the first steps of intrathymic lymphopoiesis.

Animals↗
PubMed1984

Molecular probes of phylogeny and biogeography in toads of the widespread genus Bufo.

Genetic relationships among 25 species of Central and South American Bufo and among representative North, Central, and South American, Asian, and African Bufo were probed, using the quantitative immunological technique of microcomplement fixation (MC'F) which indicated a clear separation of North, Central, and South American lineages of Bufo. The South American lineage likely diverged from the Central and North American lineages in the Eocene; the latter two lineages diverged later, probably in the mid-Oligocene. Some species groups of South American toads, defined on the basis of traditional morphological studies, are genetically quite similar within groups, whereas others are genetically divergent. The amount of albumin evolution does not appear to parallel the amount of karyotypic, morphological, ecological, or behavioral evolution documented. Comparisons suggest that the African lineages separated from the American and Asian lineages in the late Cretaceous, corresponding to the time of the final separation of Gondwanaland, the southern supercontinent including the modern continents of South America, Africa, Australia, Antarctica, and India. The Asian lineages diverged from the lineage giving rise to all of the American species in the early Paleocene.

Animals↗
PubMed1976

[The evolutionary principle in histology].

The A.A. Zavarzin's law of parallel lines in tissue evolution showing the appearance of a common tissue organization pattern is the major regularity of the cellular development of animals in phylogenesis. It carries out the metabolism principally similar in all animals in their interaction with the environment. The A.A. Zavarzin's law of parallel lines is also the main regularity of the evolution of tissue interrelations bringing about the principal processes of metabolism. The tissue evolution as well as the evolution of the organism is under the influence of factors of heredity, variability and natural selection. These factors however have an influence mediated by the organism evolution. The precess of cephalization represents a fairly important manifestation of the evolution of animals. The theory of general histogenesis reflects the main regularity of the cellular development in ontogenesis of man and animals. Being a further development of the conception of the A.A. Zavarzin's tissue evolution this theory shows the development of the animal cellular structure as a single general process of histogenesis, beginning with a zigote and continuing till the end of the organism life. The integration, heterochronia and determination manifest themselves in this process of differentiation of cells, tissues and intertissue relations.

Biological Evolution↗
PubMed1976

[Several methodologic problems of evolutionary histology in light of the findings of molecular genetics].

The paper elucidates certain methodological problems of evolutionary histology. The principal attention is given to the necessary synthesis of modern molecular biology and genetics and evolutionary histology. Modern data on the levels of the organization of the living matter and their significance for the rightness of the A.A. Zavarzin's theory of parallel lines in the tissue evolution are presented. The hypothesis of an application of the theory of parallel lines in the hereditary variability by N.I. Vavilov to the analysis of regularities of the tissue evolution is set forth. The hypothesis is proposed that mutation changes of similar genes in representatives of different types of animals underlie the regularities of the tissue evolution discovered by A.A. Zavarzin, and epigenomic changes of regulation systems occurring most frequently in the process of ontogenesis of organisms lie in the basis of the divergent evolution of tissues after N.G. Chlopin.

Biological Evolution↗
PubMed2024

Massively parallel approaches for characterizing noncoding functional variation in human evolution.

The genetic differences underlying unique phenotypes in humans compared to our closest primate relatives have long remained a mystery. Similarly, the genetic basis of adaptations between human groups during our expansion across the globe is poorly characterized. Uncovering the downstream phenotypic consequences of these genetic variants has been difficult, as a substantial portion lies in noncoding regions, such as cis-regulatory elements (CREs). Here, we review recent high-throughput approaches to measure the functions of CREs and the impact of variation within them. CRISPR screens can directly perturb CREs in the genome to understand downstream impacts on gene expression and phenotypes, while massively parallel reporter assays can decipher the regulatory impact of sequence variants. Machine learning has begun to be able to predict regulatory function from sequence alone, further scaling our ability to characterize genome function. Applying these tools across diverse phenotypes, model systems, and ancestries is beginning to revolutionize our understanding of noncoding variation underlying human evolution.

Humans↗
PubMed1991

Digestive histochemical reactions in rats after space flight of different duration.

Different histochemical reactions were searched in the digestive tract of rats that flighted on Soviet biosatellites, 5, 7, 13, 14 and 18 1/2 days (2). Space flight decreased glycoprotein (GP) content of sublingual glands and of gastric and intestinal mucosa, and increased reactions for leucin-aminopeptidase (LAP) and acid phosphatase (ACP) of the small intestine. These responses were in relation with the duration of the flight. For searching some possible mechanism by which they occurred, same investigations were done in rats submitted at soil level to a contention hypokinesia (HK), for mimicking space flight. After HK, similar histochemical responses were founded as after the true flight. The evolution of histochemical responses paralleled the corticosterone hypersecretion, suggesting a causal correlation, but they were also the same in adrenalectomised rats. Effectory hormonal pathways are thus further to be searched, as well as a correlation with the intermediary metabolism, as a similar evolution was founded in pancreatic, insulin secreting, B cells.

Animals↗
PubMed1992

Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix.

The ability of chondrocytes from calf articular cartilage to synthesize and assemble a mechanically functional cartilage-like extracellular matrix was quantified in high cell density (approximately 10(7) cells/ml) agarose gel culture. The time evolution of chondrocyte proliferation, proteoglycan synthesis and loss to the media, and total deposition of glycosaminoglycan (GAG)-containing matrix within agarose gels was characterized during 10 weeks in culture. To assess whether the matrix deposited within the agarose gel was mechanically and electromechanically functional, we measured in parallel cultures the time evolution of dynamic mechanical stiffness and oscillatory streaming potential in uniaxial confined compression, and determined the intrinsic equilibrium modulus, hydraulic permeability, and electrokinetic coupling coefficient of the developing cultures. Biosynthetic rates were initially high, but by 1 month had fallen to a level similar to that found in the parent calf articular cartilage from which the cells were extracted. The majority of the newly synthesized proteoglycans remained in the gel. Histological sections showed matrix rich in proteoglycans and collagen fibrils developing around individual cells. The equilibrium modulus, dynamic stiffness, and oscillatory streaming potential rose to many times (>5x) their initial values at the start of the culture; the hydraulic permeability decreased to a fraction (approximately 1/10) that of the cell-laden porous agarose at the beginning of the culture. By day 35 of culture, DNA concentration (cell density), GAG concentration, stiffness, and streaming potential were all approximately 25% that of calf articular cartilage. The frequency dependence of the dynamic stiffness and potential was similar to that of calf articular cartilage. Together, these results suggested the formation of a mechanically functional matrix.

Animals↗
PubMedDate not supplied

[The evaluation of the measurement of serum fibronectin in pulmonary tuberculosis].

The investigation was carried out in 125 patients with pulmonary tuberculosis in different stages of evolution. The treatment was that granted, used in triple and/or quadruple scheme twice a week. In the greatest part of the patients the concentration of serum fibronectine (sFN) was followed in its dynamics. A reasonable increase (statistical average) of the sFN was found in the patients with tuberculosis (tbc), active at the first treatment. The values regressed slowly, parallel to the favourable evolution under treatment. In the chronic forms, values situated at the normal or at the inferior limit were recorded. They were probably due to the sum of factors often met in these patients: protein-caloric malnutrition, chronic alcoholism with afferent hepatopathies, nonspecific chronic bronchial suppurations. No significant correlation of the sFN concentration was noticed in relation to the radiologic extension of the lesions, to the structure of the chemotherapeutic regimen, or to age. There exists a large variability of the sFN concentration in tbc, both at the beginning and during chemotherapy. The sFN level is not enough for the assessment of the disease stage or evolution; for increasing its informational value, the concentration of the immune circulatory complexes (ICC) and the lymphocytic subsets T were investigated.

Adolescent↗
PubMed1976

[Clinical, functional and hemodynamic course in patients with chronic bronchitis at the stage of chronic cor pulmonale].

Twenty seven patients, almost all chronic bronchitic, and with a "chronic cor pulmonale" according to the E. C. G., were followed clinically, radiologically and for E. C. G. and pulmonary functions, and also for the hemodynamics, during a minimum of 3 years, the average length of observation period being about 5 years. Twelve patients died during this observation time. Periods of right heart failure (R. H. F.) were frequent : 3.6 +/- 3.0 in average, slightly more frequent in the deceased patients than in the others. The average delay between the onset R. H. F. and death was of 49.3 +/- 30.8 months ; the survivors on average lived another 54.6 +/- 30.8 months after their first R. H. F. The mean pulmonary arterial pressure (PAP) was quite stable, going from 27.5 +/- 7.0 to 31.2 +/- 9.6 torr (an unsignificicant difference); in only 9 cases did the PAP increase of more than 5 torr during the observation period (acute attacks excepted). The PAP evolution was not significantly different in the deceased and the survivors. PAP worsening by steps after a fit of R. H. F. was observed in only 4 cases. Chronological variations of PAP were well correlated with those of Pao2 during the same period : r = -- 0.68, P less than 0.001. The hemodynamic evolution (PAP), that of the E. C. G. and the volume of the heart were reasonably parallel to the overall clinical evolution ; the E. C. G. evolution had the closest match with the overall clinical evolution (78% of cases). The E. C. G. enables only a late diagnosis of CCP but its evolution is very valuable for prognosis. Hemodynamic tests have a double value initially for diagnosis and later for the evolution.

Adult↗
PubMed2026

Virulent Parasites Emerge in Hosts With Rising Temperatures.

Climate change is increasing the risk of emerging parasites. However, whether more virulent variants will spread during climate-driven outbreaks remains unclear. Here, we aimed to explore the short-term trajectory of parasite evolution-at the phenotypic and genomic scales-across environmentally relevant temperatures in a thermally mismatched host-parasite interaction. We experimentally evolved a wild parasitic bacterium (Leucobacter musarum), across the thermal range (20°C-30°C) and extremes (35°C) of Cabo Verde-the site of field collection-in a Caenorhabditis elegans host strain. Starting from a single bacterial isolate, we then tracked phenotypic and de novo genomic changes that arose across replicate populations following ten passages of experimental evolution. We found that at 25°C, warm for the host but an average temperature for the parasite, host-mediated selection favoured higher virulence and genomic diversification by the end of the experiment. At hot temperatures, towards the limit of host survival, virulence was maintained across all parasite populations. Parasites evolved at hot temperatures also displayed a latent virulence boost, deadlier once hosts experienced a heatwave. Patterns of molecular evolution were constrained to parallel changes in fewer loci at extreme temperatures. Our findings suggest that shifting environmental temperatures will leave phenotypic and genomic signatures on evolving parasites.

Animals↗
PubMed1974

The importance of gene rearrangement in evolution: evidence from studies on rates of chromosomal, protein, and anatomical evolution.

We have compared the relative rates of protein evolution and chromosomal evolution in frogs and mammals. The average rate of change in chromosome number has been about 20 times faster in mammals than in frogs. Whereas it takes only 3.5 million years, on the average, for a pair of mammal species to develop a difference in chromosome number, the corresponding period for frogs is 70 million years. In contrast, the rate of protein evolution in mammals has been roughly equal to that in frogs. The rapid rate of gene rearrangement in mammals parallels both their rapid anatomical evolution and their rapid evolutionary loss of the potential for interspecific hybridization. Thus, gene rearrangements may be more important than point mutations as sources for evolutionary changes in anatomy and way of life.

Adaptation, Biological↗
PubMed1976

Spastic paraplegia associated with Addison's disease: adult variant of adreno-leukodystrophy.

Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occassionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of "epitheloid" histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive stroge of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes. In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to "classical" ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocyte infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.

Addison Disease↗